Cardiac preload

Definitions & Key takeaways

Cardiac preload is the extent to which the left ventricular wall stretches at the end of diastole, or before systole starts. The amount of left ventricular wall stress is directly proportional to the ventricular end-diastolic pressure and the radius of the left ventricle, and indirectly proportional to two times the thickness of the left ventricular wall. Factors that increase preload include an increase in venous return (due to increased venous pressure or increased heart rate), an increase in arterial elastance, or an increase in myocardial contractility. Factors that affect preload include venous return, atrial contraction, heart rate, resistance from valves, and ventricular compliance.

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Introduction0:00–0:52

Cardiac preload is one of the main factors that influence how much blood the heart pumps out with each heartbeat, or stroke.
Now, remember that the heart has two upper chambers: the left atrium, which receives oxygenated blood from the lungs via the pulmonary veins; and the right atrium, which receives deoxygenated blood from all of our organs and tissues via the superior and inferior vena cava.
From the atria, the blood flows into the lower chambers of the heart: the left ventricle, which pumps oxygenated blood to all our organs and tissues via the aorta; and the right ventricle, which pumps the deoxygenated blood back to the lungs via the pulmonary arteries.
Alright, now, each heartbeat consists of two phases: systole, which is when the heart contracts and pumps the blood out of the ventricles; and diastole, which is when the heart relaxes and ventricles fill with blood.

Heartbeat Phases0:52–1:24

And as the left ventricle fills with blood during diastole, the pressure within it rises. The pressure at the end of diastole is called the left ventricular end-diastolic pressure, which is a key determinant of cardiac preload.
So, cardiac preload can be defined as the ventricular wall stress at the end of diastole. And it can be calculated using the law of Laplace, which states that wall stress = pressure (P) x radius (R) / 2 x wall thickness (W).

Cardiac Preload1:24–2:44

Another way to say this is that cardiac preload is directly proportional to the end-diastolic pressure and radius of the left ventricle, and indirectly proportional to two times the ventricular wall thickness.
To visualize this, let’s look at a cross-section of the left ventricle, which looks a bit like a doughnut, with little dough.
A diet doughnut, if you will. Now, the little dough circle represents the wall of the left ventricle, and its thickness is the ventricular wall thickness, or W.
Pressure, or P, on the other hand, is determined by the volume of blood inside the ventricle at the end of diastole. And finally, the radius, is the distance from the center of the ventricle to the outer edge.
So...actually, the radius, or R, comprises of an inner radius, or Rin, which is the radius of the ventricular cavity, and the full radius is Rin plus the ventricular wall thickness.

Left ventricular end-diastolic radius2:44–3:21

And if you thought we were done with math, hold your horses. There’s one more formula we need to calculate the inner radius, which is: Rin=3 square root 3V / 4π, where V is the volume of the left ventricle at the end of diastole, or Rin = (3V/4π)⅓.
And then we can add wall thickness to the inner radius to determine the left ventricular end-diastolic radius, or R. Alternatively, preload can be defined as the length of muscle fibers, or sarcomeres, at the end of diastole.

Sarcomeres3:21–5:22

So let’s zoom in on the wall of the left ventricle. The bulk of these walls is made up of short, branched cardiac muscle cells packed one next to the other.
Zooming in further, if we look inside the muscle cells, we see bundles of myofibrils, or long chains of sarcomeres. The sarcomere is the smallest structure in the muscle that is capable of contracting so it's considered the basic contractile unit of the muscle.
Zooming in further, you can see that the sarcomere has two Z discs that form its boundary and an M line in the middle. Attached to the Z disc are thin filaments made of actin protein.
These actin filaments have structural polarity which means the end of the filament look different from one another. We can think of it like an arrow with the pointed end being the “minus end,” pointing towards the M line, and the tail end being the “plus end,” attached to the Z disc.
Just like an arrow, the actin filament can only move in one direction: the direction it’s pointed at. Attached to the M line are the myosin filaments which are thick bundles of myosin proteins with two globular heads.
During a muscle contraction, the myosin heads grab onto the actin filaments, and pull them towards the M line which brings the two Z discs closer together.
So, the length of the sarcomere is important because the force of contraction during systole depends on the number of myosin heads that bind to actin.
This number directly depends on the length of the overlapping section between actin and myosin filaments. And the length of the overlapping section depends on the overall length of the sarcomere.
But, no matter how we choose to define cardiac preload, the problem is that these measurements are not possible in practice.

Left ventricular end-diastolic Volume5:22–6:22

Imagine trying to measure the length of sarcomeres in vivo! Therefore, in clinical practice, a surrogate for cardiac preload is used - specifically, the volume of blood within the left ventricle at the end of diastole that stretches out the overall muscle wall and each sarcomere within it.
It’s important to note that the end-diastolic left ventricular volume is not the same as cardiac preload; but it can be measured with an echocardiogram, so it’s easier to use this parameter in practice.
Now, the left ventricular end-diastolic volume and therefore preload is affected by five factors: venous pressure and rate of venous return, atrial contraction, resistance from valves, ventricular compliance, and heart rate.
First, let’s focus on venous pressure and the rate of venous return. Venous pressure and the rate of venous return are influenced by two other factors: venous tone and circulating blood volume.

Venous Pressure6:22–6:36

Now, venous tone is determined by vasodilating and vasoconstricting factors. Vasodilating factors relax smooth muscle cells within the vein walls, thereby decreasing the vascular tone of the vein.

Venous Tone6:36–8:59

One such vasodilating factor is atrial natriuretic peptide, or ANP, which is secreted by cardiac muscle cells in the walls of the atria in response to an increased circulating blood volume that makes an increased amount of blood reach and distend the atrium.
When ANP is secreted and venous tone decreases, that results in peripheral pooling of the blood and decreased return of the venous blood to the heart.
Moreover, the decreased return of the venous blood leads to decreased left ventricular pressure and decreased end-diastolic volume and therefore decreased cardiac preload.
Another way to visualize this is through pressure-volume loops, which are graphs that show the pressure inside the left ventricle on the y axis, and the volume of blood inside the left ventricle on the x axis.
And the green dotted loop represents the variation over the course of one cardiac cycle under normal circumstances. When vasodilating factors are secreted and cardiac preload is decreased, left ventricular pressure and end-diastolic left-ventricular volume both decrease, so the loop shifts to the left.
On the other hand, vasoconstricting factors, such as sympathetic stimulation during the fight-or-flight response, constrict smooth muscle cells within the vessel walls, thereby increasing the vascular tone of the veins.
This results in an increased venous return to the heart. Eventually, this leads to an increased end-diastolic volume and therefore increased cardiac preload, which helps send more oxygenated blood to organs and tissues.
This might come in handy if a pack of kangaroos started chasing you at the mall! And if we look back at our pressure-volume loops, increased left ventricular pressure and end-diastolic volume, and the resulting increased cardiac preload shifts the loop to the right.

Circulating Blood8:59–10:02

Speaking of which, the amount of circulating blood volume also influences venous pressure and venous return rate. Now, an average adult has a circulating blood volume of 5 liters, but in different conditions, this volume of blood can change.
On the one hand, circulating blood volume can decrease in the context of dehydration or blood loss following an injury, and this is called hypovolemia or volume depletion.
Hypovolemia leads to decreased end-diastolic volume and therefore decreased preload. On the other hand, circulating blood volume can increase, which is called hypervolemia, or fluid overload.
One cause of this is when too much intravenous fluids are given to an individual - also known as transfusion overload. Eventually, more fluids in the circulatory system will result in an increased end-diastolic volume and therefore increased preload.

Atrial Contraction10:02–10:41

Next factor is atrial contraction. Increased force of atrial contraction, either by sympathetic stimulation of the heart or increased filling of the atria, increases the volume of blood that enters the ventricle, eventually causing an increase in end-diastolic volume, or EDV, and preload.
On the other hand, when the atria can’t pump blood efficiently and in sync, which is common in atrial arrhythmias, the volume of blood that enters the ventricle will decrease, eventually causing a decrease in end-diastolic volume and preload.
Ok, next up, there’s resistance from valves. This refers to the inflow valves, that connect the atria and the ventricles, such as the mitral valve on the left and the tricuspid valve on the right, and the outflow valves, which connect the left and right ventricle to the aorta, and the pulmonary artery, respectively.

Valve Resistance10:41–11:41

Inflow resistance is created by the narrowing of atrioventricular valve openings, such as mitral stenosis and tricuspid stenosis.
This results in decreased filling of the ventricles and therefore decreased preload. On the other hand, outflow resistance is created by the narrowing of aortic and pulmonic valves, such as aortic stenosis and pulmonary stenosis.
Eventually, this results in decreased emptying of the ventricles and therefore increased preload. Next factor is ventricular compliance, which is, simply said, the flexibility of the ventricles.

Ventricular Compliance11:41–12:05

Compliant, stretchy ventricles, such as seen in dilated cardiomyopathy, increase preload; while noncompliant, stiff ventricles, such as seen in ventricular hypertrophy, decrease preload.

Heart Rate12:05–12:23

And finally, there’s heart rate. Normal heart rate, 60-100 beats per minute, allows adequate time for ventricles to fill, while abnormal heart rate, such as fast heart rhythm, or tachycardia, reduce the filling time, eventually decreasing preload.
Alright, as a quick recap. Preload is defined as the ventricular wall stress at the end of diastole.

Review12:23–13:17

Through the law of Laplace, we can say that wall stress is directly proportional to the ventricular end-diastolic pressure and radius, and indirectly proportional to two times the ventricular wall thickness.
Alternatively, preload can be defined as the length of muscle fibers, or sarcomeres, at the end of diastole. But since these definitions are more theoretical, in clinical practice, the end-diastolic volume is used to assess cardiac preload.
Finally, the end-diastolic volume and therefore preload is affected by five factors: venous pressure and rate of venous return, atrial contraction, resistance from valves, ventricular compliance, and heart rate.